TACI expression and plasma cell differentiation are impaired in the absence of functional I?BNS.

ABSTRACT: Impaired classical NF-?B pathway signaling causes reduced antibody responses to T-independent (TI) antigens. We investigated the potential reasons for defective TI responses in mice lacking the atypical inhibitory kappa B (I?B) protein of the NF-?B pathway, I?BNS. Analyses of the plasma cell compartment in vitro and in vivo after challenge with lipopolysaccharide (LPS) showed significant decreases in the frequencies of plasma cells in the absence of I?BNS. In vitro activation of B cells via the B cell receptor or via Toll-like receptor 4 revealed that early activation events were unaffected in I?BNS-deficient B cells, while proliferation was reduced compared to in similarly stimulated wildtype (wt) B cells. I?BNS-deficient B cells also displayed impaired upregulation of the transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), which is essential for TI responses, and decreased sensitivity to TACI ligands upon stimulation. Furthermore, I?BNS-deficient B cells, in contrast to wt B cells, displayed altered expression of IRF4, Blimp-1 and Pax5 upon LPS-induced differentiation, indicating impaired transcriptional regulation of plasma cell generation.

SUBMITTER: Khoenkhoen S 

PROVIDER: S-EPMC6850186 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature